US2072829A - N-metbrax-c - Google Patents
N-metbrax-c Download PDFInfo
- Publication number
- US2072829A US2072829A US2072829DA US2072829A US 2072829 A US2072829 A US 2072829A US 2072829D A US2072829D A US 2072829DA US 2072829 A US2072829 A US 2072829A
- Authority
- US
- United States
- Prior art keywords
- weight
- allyl
- parts
- isopropyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229960003153 aprobarbital Drugs 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- -1 allyl halides Chemical class 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000005749 Copper compound Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
Definitions
- N-methyl-C,C-allylisopropyl-barbituric acid possesses valuable therapeutic properties. I'he new compound is particularly well suited for narcotic purposes.
- N-methyl-C,C-allyl-isopropyl-barbituric acid is obtained by the action of methylating agents on C,C-allyl-isopropyl-barbituric acid, of allyl halides on N-methyl-C-isopropyl-barbituric acid or of methyl-carbamide on allyl-isopropyl-malonicester.
- N-methyl-C,C-allyl-isopropyl-barbituric acid melts at 56-57 C. It is easily soluble in the usual organic solvents, difficultly soluble in water and is to be used for therapeutic purposes.
- Example 1 210 parts by weight of C,C-allyl-isopropyl-barbituric acid are dissolved in 1300 parts by weight of water and 118.7 parts by weight of 33.7% sodium hydroxide solution. While stirring 126 parts by weight of dimethyl sulphate are dropped into the solution. Reaction takes place immediately with evolution of heat. The reaction product is precipitated as an oil. For removing small quantities of tetra-alkyl-barbituric acid which may be present, the reaction product is treated with 118.7 parts by weight of 33.7% sodium hydroxide solution, whereby the tri-alkylbarbituric acid is again dissolved. The tetraalkyl-barbituric acid may then be removed by filtration or extraction.
- N-methyl-C,C-allyl-isopropyl-barbituric acid is precipitated by the addition of acid. It may be purified by distillation in vacuo (boiling point l76-178 C./ 12 mm.), or by crystallization from dilute alcohol or petroleum ether and melts at 56-57 C.
- the whole quantity of sodium hydroxide solution may also be added at the beginning without detrimental effect on the methylation with di- Example 2 184 parts by weight of N-methyl-C-isopropylharbituric acid are dissolved in 900 parts by Weight of water and 133 parts by weight of 30% sodium hydroxide solution. Hereafter 121 parts by Weight of allyl bromide are added and stirred at 30-35 C. until the allyl bromide has disappeared.
- the N-methyl-C,C-allyl-isopropyl-barbituric acid thus obtained is purified either by distillation in vacuo (boiling point 176-173 C./12 mm.) or by crystallization from dilute alcohol or petroleum ether.
- the transformation may be carried out more quickly and. at a lower temperature if small quantities of copper or of copper compounds are added as described in the process of German Patent No. 526,854.
- Example 3 To a solution of 57 parts by weight of sodium in 630 parts by weight of absolute alcohol 110 parts by weight of methyl carbamide and 242 parts by weight of isopropyl-allyl-malonic-ester are added. The Whole mixture is heated for 6-8 hours in an autoclave to C. The alcohol is then removed by distillation. The residue is dissolved in ice Water and acidified after filtration. The precipitated Nmethyl-C,C-allyl-isopropyl-barbituric acid is purified either by distillation in vacuo or by crystallization from dilute alcohol or from petroleum ether.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Patented Mar. 2, 1937 EATT OFFEE Otto Schnider, Basel, Switzerland, assignor to Hoifrnann-La Roche Inc, Nutley, N. 3., a corporation of New Jersey No Drawing. Application May 8, 1936, Serial No. 78,733. In Switzerland May 17, 1935 1 Claim.
It has been found that N-methyl-C,C-allylisopropyl-barbituric acid possesses valuable therapeutic properties. I'he new compound is particularly well suited for narcotic purposes.
5 By intravenous injection of aqueous solutions of the sodium salt deep narcosis is obtained which by further slow injection may be kept at the profound stage necessary for surgical operations.
N-methyl-C,C-allyl-isopropyl-barbituric acid is obtained by the action of methylating agents on C,C-allyl-isopropyl-barbituric acid, of allyl halides on N-methyl-C-isopropyl-barbituric acid or of methyl-carbamide on allyl-isopropyl-malonicester.
N-methyl-C,C-allyl-isopropyl-barbituric acid melts at 56-57 C. It is easily soluble in the usual organic solvents, difficultly soluble in water and is to be used for therapeutic purposes.
Example 1 210 parts by weight of C,C-allyl-isopropyl-barbituric acid are dissolved in 1300 parts by weight of water and 118.7 parts by weight of 33.7% sodium hydroxide solution. While stirring 126 parts by weight of dimethyl sulphate are dropped into the solution. Reaction takes place immediately with evolution of heat. The reaction product is precipitated as an oil. For removing small quantities of tetra-alkyl-barbituric acid which may be present, the reaction product is treated with 118.7 parts by weight of 33.7% sodium hydroxide solution, whereby the tri-alkylbarbituric acid is again dissolved. The tetraalkyl-barbituric acid may then be removed by filtration or extraction. From the solution of its sodium salt N-methyl-C,C-allyl-isopropyl-barbituric acid is precipitated by the addition of acid. It may be purified by distillation in vacuo (boiling point l76-178 C./ 12 mm.), or by crystallization from dilute alcohol or petroleum ether and melts at 56-57 C.
The whole quantity of sodium hydroxide solution may also be added at the beginning without detrimental effect on the methylation with di- Example 2 184 parts by weight of N-methyl-C-isopropylharbituric acid are dissolved in 900 parts by Weight of water and 133 parts by weight of 30% sodium hydroxide solution. Hereafter 121 parts by Weight of allyl bromide are added and stirred at 30-35 C. until the allyl bromide has disappeared. The N-methyl-C,C-allyl-isopropyl-barbituric acid thus obtained is purified either by distillation in vacuo (boiling point 176-173 C./12 mm.) or by crystallization from dilute alcohol or petroleum ether.
The transformation may be carried out more quickly and. at a lower temperature if small quantities of copper or of copper compounds are added as described in the process of German Patent No. 526,854.
Example 3 To a solution of 57 parts by weight of sodium in 630 parts by weight of absolute alcohol 110 parts by weight of methyl carbamide and 242 parts by weight of isopropyl-allyl-malonic-ester are added. The Whole mixture is heated for 6-8 hours in an autoclave to C. The alcohol is then removed by distillation. The residue is dissolved in ice Water and acidified after filtration. The precipitated Nmethyl-C,C-allyl-isopropyl-barbituric acid is purified either by distillation in vacuo or by crystallization from dilute alcohol or from petroleum ether.
1 claim:
N-methyl-C,C-allyl-isopropyl-barbiturio acid melting at 56-57 C., boiling at 176-178" C./12 mm., being easily soluble in the usual organic solvents and possessing valuable therapeutic properties.
OTTO SCHNIDER.
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2072829A true US2072829A (en) | 1937-03-02 |
Family
ID=3428537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US2072829D Expired - Lifetime US2072829A (en) | N-metbrax-c |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2072829A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2868790A (en) * | 1959-01-13 | Manufacture of barbituric compounds |
-
0
- US US2072829D patent/US2072829A/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2868790A (en) * | 1959-01-13 | Manufacture of barbituric compounds |
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